Liposomes are widely described in the literature, and their structure is well known. Typically, they have an onion-like multilamellar structure comprising a plurality of lipid bilayers spaced one from another by aqueous material. Another type of liposome is a unilamellar liposome, sometime referred to as a vesicle, which is a single lipid bilayer disposed about an aqueous material.
The use of liposomes as carriers or vehicles for drugs is known, and can be achieved by a variety of methods. One method involves casting a film of lipid by evaporation from a solution in an organic solvent, for example chloroform, and then dispersing the film in a suitable aqueous medium. In the case of lipid-soluble biologically active compounds, that is, those which associate with the lipid layers rather than the aqueous phase of the liposomes, the compound can be cast as a film together with a phospholipid, using a common organic solvent. A disadvantage of this method is that the amount of active compound that can be incorporated into the lipid bilayer is limited. Additionally, the casting method can not be scaled up to accommodate large batches. In the case of water-soluble biologically active compounds the compound is typically associated with liposomes by dispersing a cast lipid film with an aqueous solution in which the compound is solubilized. Disadvantages of this method include the difficulty of incorporating sufficient quantities of the active compound in the vesicles, and instability and shelf life of the dispersion. Another disadvantage of this method is the presence of trace amounts of solvent used in the creation of the vesicles.
The loss of the biologically active compound from liposomes into external aqueous medium is another factor which restricts the potential of these preparations as practical dosage forms. This is particularly the case for not only low molecular weight, water-soluble compounds, but also for lipid-soluble compounds, both of which can partition into the external aqueous medium until equilibrium is reached. If the concentration of compound is small, and/or the volume of the external aqueous medium is large, this loss can represent a significant proportion of the total amount of the biologically active compound in the liposomes.